정량적 구조-활성 상관 관계와 생리학 기반 약물동태를 사용한 새로운 선도물질 최적화 전략

Novel Lead Optimization Strategy Using Quantitative Structure-Activity Relationship and Physiologically-Based Pharmacokinetics Modeling

The purpose of this study is to demonstrate how lead compounds are best optimized with the application of in silico QSAR and PBPK modeling at the early drug discovery stage. Several predictive QSAR models such as IC50 potency model, intrinsic clearance model and brain penetration model were built and applied to a set of virtually synthesized library of the BACE1 inhibitors. Selected candidate compounds were also applied to the PBPK modeling for comparison between the predicted animal pharmacokinetic parameters and the observed ones in vivo. This novel lead optimization strategy using QSAR and PBPK modelings could be helpful to expedite the drug discovery process.